Paroxetine For Hot Flashes - A Potential Problem

This opinion piece caught my eye in the New England Journal of Medicine this week for a number of reasons.  First off, it involves my least favorite antidepressant, so I am always interested in why there may be broadened indications.  I stopped prescribing paroxetine well over 20 years ago because of what I considered to be an unfavorable pharmacokinetic and side effect profile.  In this case there is a potential interaction that could decrease the efficacy of tamoxifen - a medication used to treat breast cancer.  In my capacity as a consultant, I frequently encounter people who are already on paroxetine and will continue it if that is their preference.  I do encounter people with side effects and either transition them off of the medication or onto something else depending on the clinical scenario.  Second, FDA decision-making is always interesting to follow and that is also true in this case.  Like the recent Zohydro decision, the FDA decided to go against the recommendation of its scientific committee and approve the specified name brand product for hot flashes.  Third, the remarketing for generics as brand name drugs with slightly different formulations is another interesting aspect of FDA regulation and in this case that is also true.  The product in this case is Brisdelle, a 7.5 mg tablet of paroxetine.  Paroxetine is currently available as a generic drug as 10, 20 , 30 and 40 mg immediate release tablets and 12.5, 25 and 37.5 mg controlled release preparations.    Some of the 10 mg tablets are scored allowing for an approximation of the approved product.  Another interesting pint is that this action is apparently over a year old according to this FDA release.

The scientific evidence comes down to two randomized, double-blind, placebo controlled trials of 1184 women.  Baseline moderate to severe hot flashes were occurring at a rate of about 10 per day.  The effects observed during the trial were described as modest with an overall decrease in these hot flashes by about 0.9 per day by week 12 in one study and 1.7 per day in the other.  Despite that slight effect, the women on active drug reported a meaningful difference at the end of the study and again at 6 months.

In balancing the risk rewards of this study and the regulatory decision, the FDA Reproductive Health Drugs Advisory Committee voted 10-4 against approving Brisdelle.  The authors speculate that modest efficacy and existing warnings about suicidality swayed the Advisory Committee in this vote.  I thought it was interesting that the authors consider the safety profile of paroxetine to be well established.  Paroxetine seems to be one of the most complained about medications on the Internet and a favorite of critics who consider themselves as watchdogs of the pharmaceutical industry.  In the case of Brisdelle, the formulation had side effects that did not exceed placebo.  Anyone used to prescribing selective serotonin reuptake inhibitor (SSRI) type antidepressants is aware of a possible significant discontinuation syndrome.  The authors suggest that Brisdelle does not need to be tapered if discontinued but the package insert from the web site suggests potential problems including potential discontinuation symptoms and symptoms in neonates exposed to the medication.

The authors discuss the importance of a non-hormonal agent to treat hot flashes, especially give the impact on lifestyle and risks of stroke, coronary artery disease, thromboembolism, and breast cancer.  The only current FDA approved treatment is hormonal therapy in the form of estrogen or estrogen-progestin.  The problem is that using SSRIs or SNRIs for hot flashes is already a fairly widespread practice and it is backed up to some degree by double blind controlled trials where approval by the FDA was not the goal of the study.  I did a Medline search of controlled clinical trials for hot flashes and came up with this rough collection.  If you look up the specific studies you will find some positive and some negative.  I did not look for meta-analyses.  The most interesting opinion was naturally the one that matched mine and I found it in this study.  In this study the authors correctly conclude that potent CYP2D6 inhibitors should be avoided in women taking tamoxifen and the recommendation to avoid paroxetine is being ignored.  Using a database from the Netherlands paroxetine remains a widely prescribed antidepressant.

The last reference reflects my opinion on paroxetine in general and certainly for this specific problem.  It is also an example of how the FDA could consciously avoid problems rather than sending them out into the free market and waiting for the post marketing surveillance.  That is acceptable in the case of serious conditions with no current therapies.  But this is a case of alternate therapies with scientific backing being readily available and experts in the field recommending not to use paroxetine.  I also have a concern about the impact that remarketing a generic drug with an unusual dose on the generic drug market in general.  I am thinking about the precedent of generic doxepin being remarketed as Silenor in unique dosages of 3 and 6 mg.  Most pharmacies have generic doxepin 10 mg tablets as the smallest available dose size with a liquid form that can be ordered for additional dose adjustments.  My impression is that the prescribing of doxepin in low doses has increased in general with the recognition that low doses can be used for insomnia.  Doxepin is primarily a substrate for CYP enzymes, but at some point could probably accumulate with higher doses.  If the same thing happens with paroxetine it may result in standard antidepressant doses being prescribed for hot flashes.  That could lead to more complications and potentially more drug interactions.

George Dawson, MD, DFAPA

1:  Ronald J. Orleans, M.D., Li Li, Ph.D., Myong-Jin Kim, Pharm.D., Jia Guo, Ph.D., Mahboob Sobhan, Ph.D., Lisa Soule, M.D., and Hylton V. Joffe, M.D., M.M.Sc.  FDA Approval of Paroxetine for Menopausal Hot Flashes.  N Engl J Med 2014; 370:1777-1779.

2:  Binkhorst L, Mathijssen RH, van Herk-Sukel MP, Bannink M, Jager A, Wiemer EA, van Gelder T. Unjustified prescribing of CYP2D6 inhibiting SSRIs in women treated with tamoxifen. Breast Cancer Res Treat. 2013 Jun;139(3):923-9. doi: 10.1007/s10549-013-2585-z. Epub 2013 Jun 13. PubMed PMID: 23760858.

Dangerous Medication - Part 3 - A Risk-Averse Approach To Prescribing Bupropion

Bupropion is a widely prescribed antidepressant.  It is a safe and effective medication according to the FDA.  It can be safely prescribed with a high level of success.  It is probably more widely prescribed with the advent of guidelines suggesting that it is an augmenting agent for situations where antidepressant monotherapy is ineffective.  It may also end up being used with another antidepressant if a patient is interested in using it for smoking cessation and in an off label manner for attention deficit hyperactivity disorder and to treat sexual dysfunction associated with SSRI type antidepressants.  Bupropion does have a unique position in antidepressant pharmacotherapy.  With the increased focus on electrocardiogram abnormalities, it is probably the antidepressant that  is least likely to affect the QTc interval.

Bupropion is generally well tolerated, but there are some people who develop increased anxiety, agitation and insomnia.  This people generally need to stop taking the medication or reduce the dose.  A small number of people will develop mild to moderate hypertension and depending on the situation, the medication should be discontinued or the hypertension treated.  The largest problem I see with this medication is deciding when to stop and start it based on its contraindications.  The FDA package insert (from the FDA website using the brand name) on the matter is clear:

CONTRAINDICATIONS
WELLBUTRIN is contraindicated in patients with a seizure disorder. 
 WELLBUTRIN is contraindicated in patients treated with ZYBAN® 13 (bupropion hydrochloride) Sustained-Release Tablets, or any other medications that contain bupropion because the incidence of seizure is dose dependent. 
WELLBUTRIN is also contraindicated in patients with a current or prior diagnosis of bulimia or anorexia nervosa because of a higher incidence of seizures noted in such patients treated with WELLBUTRIN. 
WELLBUTRIN is contraindicated in patients undergoing abrupt discontinuation of alcohol or sedatives (including benzodiazepines). 
The concurrent administration of WELLBUTRIN and a monoamine oxidase (MAO) inhibitor is contraindicated. At least 14 days should elapse between discontinuation of an MAO inhibitor and initiation of treatment with WELLBUTRIN. 
WELLBUTRIN is contraindicated in patients who have shown an allergic response to 
bupropion or the other ingredients that make up WELLBUTRIN Tablets

The package insert goes into some of the evidence for these contraindications, but the details seem fairly clear to me.  So why is it that the following happens?

1.  Patients who are not aware of the fact that bupropion can cause seizures.
2.  Patients who are prescribed this medication in spite of the contraindications.
3.  Patients with a past history or an active eating disorder taking this medication.
4.  Patients who are regularly drinking alcohol +/- sedative hypnotics taking this medication.
5.  Patients who have had generalized tonic clonic seizures taking this medication and the medicine is still prescribed.

I could go into much greater detail about some of the most extreme situations where this occurs, but I think it would be more instructive if I just cut to a few basic recommendations for the safe use of this medication:

1.  Do not prescribe it in the presence of contraindications.
2.  Do not prescribe it to anyone who has a known problem with alcohol or sedative abuse problems.  In fact, obtain a new history for those disorders at the time you are obtaining informed consent for the prescription and revisit the contraindications every time you increase the dose since the seizure risk increases with dose increases.
3.  Discontinue bupropion immediately if you are treating the patient for alcohol or sedative hypnotic withdrawal.  Have a serious conversation with that person about seizure risk an the FDA contraindications before restarting it.  People provided with that information quickly reassess the need for the medication and whether or not it has been helpful.
4. Discuss the warnings with the patient if they have medical comorbidity that is flagged in the package insert such as:

Hepatic Impairment: WELLBUTRIN should be used with extreme caution in patients with severe hepatic cirrhosis. In these patients a reduced dose and/or frequency is required, as peak bupropion, as well as AUC, levels are substantially increased and accumulation is likely to occur in such patients to a greater extent than usual. The dose should not exceed 75 mg once a day in these patients.

and:

The risk of seizure is also related to patient factors, clinical situations, and concomitant 
medications, which must be considered in selection of patients for therapy with WELLBUTRIN. 
Patient factors: Predisposing factors that may increase the risk of seizure with bupropion use include history of head trauma or prior seizure, CNS tumor, the presence of severe hepatic cirrhosis, and concomitant medications that lower seizure threshold. 
Clinical situations: Circumstances associated with an increased seizure risk include, among others, excessive use of alcohol or sedatives (including benzodiazepines); addiction to opiates, cocaine, or stimulants; use of over-the-counter stimulants and anorectics; and diabetes treated with oral hypoglycemics or insulin. 
Concomitant medications: Many medications (e.g., antipsychotics, antidepressants, theophylline, systemic steroids) are known to lower seizure threshold. 

5.  Seriously weigh the seizure risk of adding any medication that might lower the seizure threshold to any person who is stable on bupropion and keep that person involved of the possible seizure risk.  Do a detailed and individualized risk assessment for prescribing medications to any patients.
6.  Document the vital signs of any patient on bupropion and the trend.
7.  Do not prescribe bupropion again to anyone who has had a seizure while taking it.

I have seen bupropion prescribed in the context of all of the contraindications and warnings without seizures or other complications.  Risking a low frequency but serious complication is not the optimal way to prescribe it.  The other consideration is that the risk assessment needs to be done on an individualized basis.  A general number quoted as an average side effects from clinical trials obviously would not apply to a patient with multiple risk factors or a patient who reliably gets side effects every time he or she takes the drug.  Population based care sounds good when it is promoted by managed care companies or government agencies, but this is a good example of where that concept fails.  As I think about all of the high risk ways I have seen bupropion prescribed, I go back to the recent post on overprescriber biases and how that influences the process.  No physician trained in psychopharmacology would have these deficits on a purely cognitive level, but in the case of treatment resistant depression and a contraindication the situation may become higher risk.

That is an ideal time for consultation or referral rather than taking a chance.

If you are reading this from the patient perspective, I encourage reading the Medline Plus handout on any medication that you are taking. The FDA approved package insert is usually available on the Internet, even in the case of most generics.  I would exercise caution if you decide to study it.  In a previous post, I point out that a lot of people really don't want to know about detailed side effects in advance because they fear developing them by mere suggestion or they might avoid taking a useful medication entirely.  Some package inserts have specific "Information to the patient" that is usually designed to communicate important information.

George Dawson, MD, DFAPA

For The Last Time - Collaborative Care Is Not Psychiatric Care

I decided to post my response to the pro-collaborative care post “Experiences in Implementing Collaborative Care” by Sanchez on this blog so that it would be more readable and contain active links.  In reading this blogpost and the accompanying links it is apparent to me that these models have little to do with psychiatry.  The link to the article by Sanchez and Adorno describes a psychiatrist who is in clinic for direct consultation with patients for 4 hours per week and is otherwise available for curbside consultation.  Contrary to some of the initial responses this requires no special training on the part of psychiatrists.  Psychiatrists currently do that every day.  The other element that jumps out of this material is that this is behavioral health or in other words managed care.  Take the psychiatrist out of the picture and you have a method for providing more detailed primary care and supportive services to patients with mild if any psychiatric illness.  Given managed care’s lack of physician time with patients this is certainly a good idea.  It might actually save psychiatrists time when they find themselves explaining medications and drug interactions for medications prescribed by primary care physicians. Promoting this as psychiatric care and suggesting that this is the future of psychiatry (see Worcester) is a clear mistake.  At the level of large healthcare organizations, it allows them to say that they are providing “behavioral health care” while the needs of patients with severe mental illnesses are neglected and their care is shifted to another system that may include a local jail.

I was trained to do collaborative care in the Assertive Community Treatment (ACT) model of Test and Stein in 1987.  For three years following residency, I did collaborative care with a case management team out of a community mental health center.  We provided comprehensive medical and psychiatric care to every person on the team and that included determining medical needs and making referrals for testing and treatment if I felt the patient’s medical problems were not being addressed.  In that model of care, the psychiatrist is a physician coordinating medical and psychiatric care for people with severe mental illnesses and significant medical comorbidity.  All of the care comes from a personal relationship with each patient.  The psychiatrist sees the patient frequently and knows them well.  We were tremendously successful in helping people stay out of hospitals, helping them live independently, providing 24/7 crisis coverage, reducing the total amount of medications prescribed, and getting them medical care for significant problems that were misdiagnosed or that they had refused to get care for. As far as I know, the community psychiatry models are being taught in most residency programs and the number of these programs has increased significantly since I was trained.

The problem with current models of collaborative care is that the psychiatrist does not or provides minimal medical or psychiatric care.  One central question is – what model are we talking about? The original model in a JAMA article points out that the psychiatrist does not see the patient at all but reviews rating scales.  The new model from a group consulting to the American Psychiatric Association (APA), has put the psychiatrist in the role of seeing the occasional patient, probably similar to the link to the Sanchez and Adorno article.  The remaining links are less specific.

The responsibilities outlined in both the AMA and APA models are not really psychiatry.  Instead they can be seen as an extension of a process initiated 20 years ago by managed care companies to ration access to psychiatrists and psychiatric care.  Everybody reading this knows what that means.  We currently have no useful inpatient treatment besides crisis care based on “dangerousness” criteria.  The largest psychiatric hospitals in the country are county jails.  We have limited to no access to detox facilities despite being in the midst of an opiate epidemic.  Access to psychiatrists is rationed and it is not uncommon to be told that a psychiatrist will be available for a 10-15 minute discussion of medications only.  Psychotherapy that resembles the psychotherapy delivered in research studies is rarely if ever provided.  In their place we have models where patients fill out a checklist and get placed on a medication as soon as possible.  That is occurring in the context of clear evidence that in many cases antidepressants already exceed the actual diagnosis of major depression.  It also occurs in the context that depression screening has no evidence basis and in most cases screening equates with diagnosis.

The current models of collaborative care can easily be done without a psychiatrist.  I think that is really the point.  Anybody can look at a PHQ-9 score and an antidepressant algorithm and put somebody on an antidepressant.  It is ironic that when psychiatrists and other physicians are being told that it is important to go through maintenance of certification procedures in addition to continuing medical education that the federal government and professional organizations have recommended such a low standard.  On the other hand it does seem like the logical conclusion of the marginalization of psychiatry and psychiatric services by the insurance industry and federal and local governments.

What is a proactive position for psychiatry?  First, recognize that this model is not the model for providing psychiatric services.  If anything it highlights the well known fact that there are two tiers of care for mental illnesses.  Psychiatrists have adapted to managed care rationing by refusing to accept insurance and changing to a cash only basis.  I recently saw this compared to how dental care is rationed and I think that is an accurate comparison.  Excellent dental care is available but the odds are the patient will pay for it.  Second, this form of rationing will probably continue the current managed care tradition of rationing psychiatric services.  It will not lead to any improvement in the availability of inpatient services, detoxification services, or psychotherapy for people with severe mental illnesses.  It will allow these companies to advertise collaborative care along with all of the other business services that are marketed as improvements to their patients.  Third, there is the undeniable connection between PHQ-9 scores and medication exposure at a time when the FDA has issued a warning on a widely prescribed antidepressant.  Fourth, with the widespread use of the PHQ-9 and availability of administrative data it is just a matter of time before somebody publishes papers based on the data showing a marked increase in the prevalence of depression.  Some researchers and many clinicians equate a PHQ-9 score with a diagnosis of depression.  Fifth, psychiatrists need to remain focused on providing a high standard of care to people with severe mental illness, neuropsychiatric problems, and people with significant medical comorbidity.  There are many internists and family physicians who are very competent in prescribing antidepressants and using typical augmentation strategies.  They are also using fewer benzodiazepines to treat anxiety disorders.  That constitutes a first line of medical care from the primary care side for mental illness in this country.

Collaborative care should not be confused with psychiatric care and psychiatrists should not be confused about this being a new model for them to follow.

George Dawson, MD, DFAPA

References:

Sharon Worcester.  Future of psychiatry may depend on integrated care.  Clinical Psychiatry News.  April 2014.  page 1.

The Model of Psychiatric Care for the Future

Collaborative Care – Even Worse Than I Imagined

     

Prior Authorization - A Legal Document?

As part of the continuous harassment that is prior authorization, I recently received a form in the mail.  It was a repeat of one that I had already signed and faxed in. The only difference was this boilerplate attached to the bottom"

"I attest that the medication requested is medically necessary for this patient. I further attest that the information provided is accurate and true, and that documentation supporting this information is available for review if requested by the claims processor, the health plan sponsor, or, if applicable, a state or federal regulatory agency. I understand that any person who knowingly makes or causes to be made a false record or statement that is material to a claim ultimately paid by the United States government of any state government may be subject to civil penalties and treble damages under both the federal and state False Claims Acts. See, e.g., 31 U.S.C. §§ 3729-3733."

I suppose I should be grateful that the PBM in this case did not attach the 14 page federal statute. And that's right, this statute is a Civil War era statute that I am sure no legislator at the time or since then would have applied to the practice of medicine. What are the implications?

1. First is the clear alliance of PBMs with the federal government. There is no clear separation of where a private for profit business ends and the government begins. I have never sent out a form or a letter with a warning that governments at any level might enforce my recommendations or services. In fact, I have complained numerous times to government officials and agencies about managed care companies at several levels only to be politely told "We can't help you." Probably because they are tripping over one another to help out the managed care cartel.

2. Secondly (and this is a recurrent theme), we have the illusion that health care companies are policing doctors and holding them accountable. That's right - the same industry that is basically one of the largest taxes on most Americans and the same industry that has dismantled mental health care and transferred the mental health care of millions of Americans to correctional facilities. There is also an implicit threat very similar to the threat I wrote about during the billing and coding era.

3. The propaganda effect - practically all managed care intrusions into the practice of medicine are designed to shift financial and clinical risk to physicians. That would includes all of the other managed care schemes like report cards, capitation, pay-for-performance, utilization review, managed formularies and all other schemes to shift risk onto doctors. The net effect of this propaganda has been to adopt the propaganda as somehow being normative. The worst effect is that these insurance companies and MBAs push the propaganda as though it is scientific fact. It not only lacks scientific merit but they frequently do not know how to analyze the data. The best example I can think of is using the PHQ-9 to "measure" depression treatment in the state of Minnesota. This is not only an invalid application of the screening tool, but the state clearly does not have any way to analyze the longitudinal data in any scientific manner.

The blizzard of propaganda from the managed care industry has been a positive for them. It has such a deleterious effect on physician morale that nobody seems to be up for a fight. They have actually launched a new wave of propaganda that is very similar to the initial wave that was used to justify managed care in the first place. We are now seeing "collaborative care" studies that claim very positive results. Medicine and psychiatry in particular seem desperate in the face of managed care propaganda. One of the front page headlines in this month's Clinical Psychiatry News was:

Future of psychiatry may depend on integrated care.


I would submit that it does but not for the reasons claimed in the article. Integrated care will result in psychiatrists with considerable less knowledge than they currently have and they will be totally marginalized without a clear set of problems to treat. The only reason psychiatrists have not been put out of business so far is that we successfully treat a set of problems that nobody else does.

Standing around in a primary care clinic looking at PHQ-9 scores and monitoring the rapid and random prescription of antidepressants by nonpsychiatrists seems like a job for an MBA rather than an MD.

I am sure at the proper time, some business type will come to that conclusion and psychiatry in managed care systems will politely disappear.........

George Dawson, MD, DFAPA

Expanding The Market For Legal Marijuana

I caught a story about the marketing of legal marijuana on public radio yesterday that was predictable in its content.  It is always interesting to observe human behavior when it comes to selling a potentially addictive intoxicant.  Suddenly - people with no interest or aptitude for science and medicine become "master growers" and gurus of the medical effects of marijuana.  It takes on an eery analogy with the business types who have taken over medicine.  Money gives you immediate legitimacy whether you know anything or not.  And really - how much do you have to know to grow and sell pot?  Feign a little concern and market it to everybody - just like tobacco.

In all of the agitation about "medical marijuana" and the gnashing of teeth in state legislatures across the land, I guess nobody was anticipating that there will now be a branding and marketing emphasis on weed.  How do you determine if 30% or your audience is minors?  The MPR story illustrates how some dealers want to differentiate their product by the people who use it.  They want to make sure that they are attracting more than "stoners".  Put it in an upscale store and market it like fine wine.  Having gone from Cheech and Chong comedy albums and movies in the 1970's to weed as a serious product is a mind expanding experience for people from my generation.  Besides getting used to the concept there are probably a couple of other things for consideration.

The issue of crime and marijuana production is real.  As a student of reality TV, there are clearly growers and dealers out there who have questionable ethics and seem to do more than just drop prices to compete with one another.  The people on reality TV seem to carry firearms and steal from one another at the minimum. It makes sense to me that with an increasing concentration of people who expect to get wealthy from selling weed, that this kind of activity will increase.  The 2009 letter from the Department of Justice on potential federal prosecution in states where medical marijuana is legal addresses this to some extent:

Typically, when any of the following characteristics is present, the conduct will not be in clear and unambiguous compliance with applicable state law and may indicate illegal drug trafficking activity of potential federal interest:

• unlawful possession or unlawful use of firearms;

• violence;

• sales to minors;

• financial and marketing activities inconsistent with the terms, conditions, or purposes of state law, including evidence of money laundering activity and/or financial gains or excessive amounts of cash inconsistent with purported compliance with state or local law;

• amounts of marijuana inconsistent with purported compliance with state or local law; 

• illegal possession or sale of other controlled substances; or

• ties to other criminal enterprises.

It seems to me that the DOJ anticipated some of this activity with medical marijuana.  I have not seen any specific guidance on legal marijuana for non-medical purposes.

What about the economic effects?  Will marijuana dispensaries become as common as liquor stores and if so does the economics of liquor stores have any implications?  Lotterman points out that liquor stores are intensely competitive businesses and no one seller has enough leverage to increase the price.  Demand is also inelastic and that means that the amount purchased does not vary significantly with any initial price increases.  Inelastic demand also occurs with food and emergency medical services.  Buyers tend to not postpone purchases based on price - at least initially.  As a result the businesses have low margins due to competition but fairly high volume and it does not take much to impact their profitability.  The article is written about the potential impact of of a law that keeps liquor stores open on Sunday.  Lotterman also talks about the cost to society of keeping the liquor stores open on Sunday.  I think that marijuana dispensaries and the dispensaries of whatever other drug the politicians legalize will eventually resemble the liquor store scenario with a proliferating collection of low margin businesses.  It will take a while for the market to get to that level, largely due to the folklore associated with the product at this point in time.    

Why is this model important?  Two reasons really.  The first is the current marketing angle.  The marijuana entrepreneurs want to expand the market including expanding it to people who are not using the product.  Secondly will be the level of availability.  If we are looking at the liquor store model, each establishment will have to move a large amount of product to stay in business.  That will involve a range of product analogous to expensive wines and liqueurs in fancy bottles to the inexpensive vodka that is the mainstay of alcoholism.  Few people will get rich,  In many ways it will be similar to the Freakonomics analysis of why it is hard to get rich selling crack cocaine.  In the end, high volume low margin business benefits the few and not the many who may end up taking the risks.   It is the ideal low cost mechanism for maximizing exposure of the product to the most people.  

I expect the learning curve on all of this to be high.  As I have watched the reality TV shows about this phenomenon as well as the dramatic adaptations like the television series Weeds it is clear that the goldrush myths are alive and well.  The product is hyped as being benign and it will be widely marketed.  It doesn't take a lot of imagination to predict that there will be crime activity associated with the overall process.  The idea that addictive intoxicants can be removed from the sphere of criminal activity so that we can all enjoy the benefits of getting high and spending the increased tax revenues is a recurrent fantasy.  There is significant criminal activity associated with the legal drugs - alcohol and tobacco and they have their own agency to deal with those problems.  

 George Dawson, MD, DFAPA

Edward Lotterman.  The Cost of Sunday Liquor Sales.  March 16, 2014.

Luke Runyon.  To Keep The Business Growing, Vendor's Rebrand Pot Stoner's Image.  Minnesota Public Radio.  April 21, 2014.  (listen to the link).

Steven D. Levitt, Stephen J. Dubner.  Why do drug dealers still live with their moms? in Freakonomics, Harper Perennial, New York, 2005, 2006, 2009: 85-113.


Supplementary 1:  I intentionally avoided any reference to the medical costs of cannabis even though we know more about that now than at any point in history.  There have been some high profile stories recently but the most believable one should come from long time cannabis advocate Tommy Chong during an interview on TMZ a few weeks ago.  I personally saw the video in real time where he comments that pot is not for everybody and that some people should avoid it.  That is a paraphrase.  I thought the actual video would be out there but it is not.  Probably too much at odds with his other videos.

Supplementary 2:  Public domain photos of marijuana courtesy of U.S. Department of Justice Drug Enforcement Administration.

Supplementary 3:  It will be an interesting twist if cannabis is marketed as anything but a drug.  That will be the difference between direct-to-consumer pharmaceutical ads where the consumer is rapidly advised of a string of significant side effects (including the possibility of death in some cases) and some ads contain the phrase: "this drug is not  for everybody" and an ad for an alcoholic beverage that says "drink responsibly".  The latter by definition will result in broader exposure for a larger number of people.

Supplementary 4:  I was just (4/30/2014) informed by a reader from Colorado that medical marijuana is still the preferred product there because the taxes on it are lower.

Overprescribing Bubble Diagram Explained

This post is intended to explain the bubble diagram that I used in the last post about overprescribing.  It focuses on the physician rather than a number of extraneous factors that are the speculative causes of overprescribing that do not make sense.  The literature on this is spotty.  There are a few references that include diagrams and purported mechanisms of overprescribing.  Before I consider those, I want to put down what I know.  The bubble by bubble explanation follows starting at the top left of the diagram - but each bubble is easily identifiable:

1.  Unconscious Motivations:  This is one of the areas that I consider to be the primary cause.  It encompasses both unconscious and preconscious causes.  The best way to look at it is with a few examples.  Overidentification with the patient seems to be a fairly common cause.  For example, a physician might have attention deficit hyperactivity disorder and realize that with treatment they were able to do much better academically.  They have a lower threshold for seeing the problem in others based on their experience.  In their medical group they are seeing many more ADHD patients than their colleagues and prescribing far more stimulant medications.  That is really a special case of the physician wanting to do something positive for the patient.  That can lead to a reduced awareness of other causes such as substance use or a person seeking cognitive enhancement and drive the prescription process.  The wish to be appreciated and have a positive relationship with the patient is another issue.  Consider the patient in clinic an uncomplicated upper respiratory infection.  Near the end of the clinical encounter, the patient senses that there will be no prescription and starts to get annoyed.  The patient talks about his or her past experience and how an antibiotic always seems to clear up their cold symptoms.  They put the physician on the defensive about the antibiotic issue and rather than argue with the patient - the physician hands over the prescription.  All of these scenarios and more reflect unconscious factors involved in prescribing and as far as I can tell this important area is untouched in the overprescribing literature.

2.  Medical knowledge:  This occurs at two levels.  The first is just the rote declarative knowledge that involves the memorization of factual knowledge about medications.  This seems like a fairly basic skill, but the amount of information we are talking about is encyclopedic.  To illustrate this all one has to do is to pull up recent FDA approved package inserts for drugs that are advertised on television.  All of the pharmacological details are presented in a neutral and highly detailed manner.  There is some prioritization in terms of  contraindications and precautions, but that is still a lot to memorize.  Experienced clinicians will still read these documents repeatedly and use summary references until they gain enough experience with the medication.  The second level is the patterns that become familiar when using the drug.  For example, after I have prescribed a drug enough times, I can tell anyone taking it what my experience with the medication is and what the experience of my patients has been.  That information is really not available anywhere else and it also can lead directly to additional testing.

3.  External validation:  The best objective source of external validation is prescribing medications according to the FDA approved indications and as instructed in those documents.  Off label prescriptions should be backed up by some data. I typically research all off label prescribing by doing Medline searches and looking for actual clinical trials looking at that application.  Example would include looking at the use of gabapentin for chronic pain and treatment of alcohol withdrawal.  Even though there are no FDA approved applications, there is ample evidence about how to use these medications, including very specific dosing recommendations.

4.  Conservative prescribing bias: My goal has always been to treat the primary problem but also eliminate or minimize problems related to the medication.  That is not the goal of some physicians.  I heard an expert in the treatment of anxiety disorders suggesting that patients needed to be treated to the point of toxicity with a medication and then the medication could be reduced.  That is not necessary as far as I can tell.  Another issue here is exceeding the FDA approved range for medication use.  Quality markers for dose range and multiple medications from the same class are nothing new and date back at least 20 years. This information is also part of informed consent and the patient should hear about it and other options at the time the change is being considered.  I have spent a lot of time correcting unnecessary high doses and polypharmacy, generally to the benefit of the patient involved.

5.  Social context:  A group of interested physicians who keep up on the research and analyze prescribing patterns is a robust safeguard against overprescribing. There are some settings for example where benzodiazepines or benzodiazepine related sleep medications are not prescribed in any circumstance.  Stimulant medications are used only by review with a colleague and the medical director and documentation on a signed form.  Such a review procedure is available to any group has utility in preventing variation in prescribing patterns and practice variation.  Practically every major clinic and hospital has a program that targets antibiotic overprescribing especially the overuse of expensive, toxic or antibiotics that are the last defense against bacteria with multiple drug resistance.  This social factor is a powerful safeguard against overprescribing.

6.   Physician as a source of information and teaching:   If the physician is in a position to teach patients about a medication they generally have a more nuanced knowledge about the medication.  They avoid stereotypes like: "When I see this problem I always prescribe this drug."  They are also aware of the likelihood of the patient recovering without the drug and the fact that any drug effect may be weak.  A classic example is low back pain in adults.  Patients generally lack knowledge about the importance of avoiding deconditioning and the need for ongoing physical therapy and back specific exercises.  They are generally surprised that conditioning provides a significant amount of pain relief.

These are a few brief examples about what can be done.  All of these dimensions occur in the context of political and regulatory influences.  For example, the FDA initiatives to approve potent opioid medications that are essentially not much different in terms of risk from current medications during an opioid epidemic.  Guidelines suggested by outside sources may not be very useful if there is insufficient evidence and the information is broadly disseminated to clinicians.  The bubbles listed on the diagram are potent factors in countering any trend that may lead to oversubscribing and they do not involve penalizing or threatening physicians - typical actions used by law enforcement or politicians that may have caused the problem in the first place.

The reader will note that I am not concerned about diagnostic proliferation.  I don't think that overprescribers do this based on the availability of new diagnoses.  I base this on my observations of the patterns that exist independently of new diagnoses and can provide a number of examples.  Physicians are trained to "do" something medical or surgical and over the course of my career that bias has not panned out in a number of areas.  Targeting that tendency will be more productive than complaining about pharmaceutical companies, diagnostic manuals, or guidelines especially when our major regulatory agency has the bias to get a drug out there for general use based on highly variable scientific evidence.  As recently noted the FDA can also ignore the recommendations of their own scientific committee.

In the end, the best assurance of adequate medical treatment and minimal risk from the treatment depends on the expertise and judgment of a physician.

George Dawson, MD, DFAPA  

Supplementary 1:  After staring at the diagram for a while I think I need to add a 7th Bubble that I would probably call "Heuristics".  It would focus on the cognitive and emotional biases that exist in prescribing.  For example,  everyone in their practice may have a person with an addiction who was subsequently able to take an addicting medication without relapsing to their primary addiction.  Is that a reason for making that a rule for prescribing?  There are a number of ways to look at potential biases in prescribing that can improve the evaluative structure of that process.

The Cure For Overprescribing

I  felt compelled to get this down because the continued wheel spinning on this subject is really starting to annoy me.  People are wringing their hands like they either don't know what to do or they angrily invoke some model that suggests a solution but not really.  The two common models invoked are the "medicalization" of society and the other is some sort of conspiracy (Big Pharma, psychiatry) to invent diagnoses and indications for prescribing medications in order for Big Pharma to make more money.  The recipients of all of the overprescribing are seen as hapless victims who never stood a chance in the face of the medicalization-conspiracy juggernaut.  All we have to do is stop the Big Pharma-monolithic psychiatry steamroller.

Some of the "solutions" to this dilemma are equally far fetched.  First of all lets say that any physicians affiliated with Big Pharma in any way need to report all of those connections.  There was recent evidence posted that this was not slowing down physician interest in these jobs - temporary or otherwise.  It is after all a free country and one where you have to make money to survive.  Physician compensation is dropping as the workload goes through the roof.  The reimbursement and hassle in psychiatry is so onerous that psychiatrists are the least likely speciality group to accept insurance.  Many physicians would like nothing better than to work for a pharmaceutical company.  So the lack of slowing down is certainly no surprise to me.  Those who are naive to the way transparency works probably thought that physicians would be too ashamed of their appearance of conflict of interest.  That is after all what we are talking about - an appearance of conflict of interest.  The prototype for transparency is the US Congress whose members blatantly take money from and provide easy access to the same industries that they regulate.  If transparency doesn't slow down Congress, why would it slow down physicians who are often in positions where they are actually being paid for rendering a service to the company and there is no evidence of  quid pro quo.

Another solution is to isolate physicians and trainees from pharmaceutical company representatives and  promotional materials.  Probably some of the weakest research in the history of the world is the research that shows that pharmaceutical promotions and advertising influences physicians to prescribe drugs.  The only weaker research is that Maintenance of Certification measures are worth the time and effort.  Not only that but by now it should be pretty clear that throwing pharmaceutical reps to the curb has not diminished the overprescribing of just about anything.  Practically all of the over prescribed antibiotics right now are generics.  The same thing is true of the overprescribed benzodiazepines and antidepressants.  As far as I can tell most of the overprescribed opioids are the usual hydrocodone/oxycodone and acetaminophen preparations and 30 mg generic oxycodone tablets.  Pharmaceutical company detailing has nothing to do with why all of these drugs are overprescribed.  Every hospital and clinic has a Pharmacy and Therapeutics Committee responsible for a formulary and they often have specific strategies to reduce costs associated with the most expensive drugs on that formulary.   I spent over a decade on two different P & T Committees.  I have never seen any member try to push through a drug - past about 20 physicians and PharmDs, based on a piece of pizza or a donut that a pharmaceutical rep gave them.  Even thinking that could happen is absurd.

What about the DSM-5 conspiracy?  What about the bereavement exclusion?  Won't that open up tens of millions of mourners to the hazards of antidepressant medications?  Only if their primary care physician is fairly clueless.  As I have previously posted psychiatrists have studied the problem and the solutions that Paula Clayton found 40 years ago are no different than today than they were then. It certainly is possible that treating rating scale results can increase antidepressant prescribing.  But that is currently considered state-of-the-art measurement based care by managed care organizations and some governments.  That is a clear force that facilitates overprescribing.

What about cognitive errors?  Do physicians really overprescribe because they lack the technical knowledge on how to prescribe?  I really doubt that is the problem.  I would cite the case of overprescribed antibiotics.  During my training and for many years after the Sanford Guide to Antimicrobial Therapy was considered definitive guidance for antibiotic therapy.  As HIV therapy increased in success and complexity an accompanying manual The Sanford Guide to HIV/AIDS Therapy came out.  Every medicine and surgery house officer and many staff counted on the microscopic type on these pages for definitive guidance on prescribing antibiotic and antiviral therapies.  It was just a question of identifying the pathogen, determining if the patient could tolerate the medication, and prescribing the drug as recommended.  So how is it possible that antibiotics are overprescribed?

So what are the real reasons for overprescribing?  The overprescribing literature extends back well over 20 years at this point.  Solutions are not readily found.  That literature generally comes down to particular class of drugs and the progress in that area.  I recently reviewed the REMS strategy to the current opioid problem and why I did not think that would work.  It really comes down to two things and neither of them has to do with a diagnosis or medicalization.  The first is that health care systems are currently set up to offer some type of test or pill as a solution to most problems.  At least when they are not claiming that they are responsible for your cradle-to-grave health and giving you a gym membership discount.  All of that goes out the window when you enter the clinic and have 5 or 10 minutes with a doctor.  In the case of mental health care, many of the conditions that present in primary care are better treated with psychotherapy than with medications, but most primary care physicians are not trained in psychotherapy.  Some are trained in motivational interviewing, but to suggest that will be successful in many of their patients is really an insult to the problems facing them.  Primary care physicians see patients with very difficult refractory problems.  These patients will see a specialist once or twice and then go back to their primary care physician for care with the same difficult problems.  Not overprescribing in many of these situations is really a question of limit setting rather than motivational interviewing.  That is especially true if the prescription is a drug that is addicting or can cause an altered state of consciousness.

The other issue is that systems of care these days, are set to run on the concept of customer satisfaction rather than excellent medical care.  The idea that a customer may not get what he or she wants is anathema to the MBAs that are currently in charge of the system.  The trickle down effect is that the physician who is setting limits on benzodiazepine, sedative hypnotics, stimulants, or opioid prescriptions will not get good customer satisfaction ratings and their compensation and role in the organization may be diminished as a result.  Health care systems that allow patients to rate their doctors on satisfaction ratings without considering that patients might be dissatisfied with reality should be held to task.

The second factor is the physician himself.  How many physicians have thought about all of the unconscious factors that lead to their overprescribing?  My guess is not many.  The problem of overprescribing is viewed as an informational deficit.  It is believed for example that teaching physicians all about chronic pain and the pharmacology of opioids will somehow reduce opioid overprescribing.  I don't see how anyone can come to that conclusion.  All physicians are taught pharmacology and most have experience prescribing opioids.  That approach seems as naive to me as the Joint Commission pain initiative in the year 2000.  Physicians need to determine for themselves why they are uncomfortable not giving a patient a prescription for whatever they are asking for.   I have heard a wide variety of reasons in my career and most of them have nothing to do with the indications for the drug.  The majority had to do with the physician believing that they could do something to alleviate the patient's distress and that wish was independent of what the diagnosis or indication for the drug was at the time.   The new variation on that theme is that physicians are somehow capable of overcoming the effects of a chronically impoverished environment, severe ongoing adversity, and either an inability or a resistance to change by prescribing a drug.  That is basically the same rationale that people use when they are addicted to drugs and alcohol.  They hope to use something to block out reality for a few hours.  Overprescribing will not change that.  The other interesting consideration is that the diagnosis is irrelevant.  It is tacked on afterwards for a prescription that is written for no real medical reason.

There needs to be better standards for determining what constitutes overprescribing and what does not.  I recently corresponded with the lead author of a paper looking at the issue overuse of health care services in the US (see reference 2).  The authors conclude that while there is ample evidence of overuse, the scope of research is limited.  Some of this is due to difficulties with definition and that would apply to the issue of overprescribing psychiatric medications.  The studies that frequently make the headlines have significant methodological problems.  A study I recently posted used two different data sources to conclude that antidepressants were being overprescribed.  The studies need to be more than prescription, survey and administrative data.  Those studies will necessarily be labor intensive and expensive.

In the end, I always come back to the informed consent model.  If the patient is competent to consent in most cases the physician and patient can have detailed conversation about the prescription including the risks and benefits and what it would like to go without it.  These are usually lengthy conversations.  These are tough decisions based on the fact that nobody wants to take medications regularly or see doctors for the purpose of continuing medications.  My own personal experience is consistent with what my patients have told me over the years - some change is desperately needed and that is often how the medication is viewed.  In that context people will often try medications with significant toxicity.  The medicines advertised on TV with death as a stated side effect are cases in point.  But no matter how much information passes, the physician needs to be the ultimate judge of whether the medication is a good idea.

It can never be a decision that is taken lightly.          

George Dawson, MD, DFAPA

1: Gordon M, Catchpole K, Baker P. Human factors perspective on the prescribing behavior of recent medical graduates: implications for educators. Adv Med Educ Pract. 2013 Jan 10;4:1-9. doi: 10.2147/AMEP.S40487. Print 2013. PubMed PMID: 23745094

2: Korenstein D, Falk R, Howell EA, Bishop T, Keyhani S. Overuse of health care services in the United States: an understudied problem. Arch Intern Med. 2012 Jan 23;172(2):171-8. doi: 10.1001/archinternmed.2011.772. Review. PubMed PMID: 22271125


Supplementary 1:  I was going to add a detailed explanation of my bubble diagram to this post but it is too long.  Look for a separate post about the bubbles.

Supplementary 2:  An updated higher resolution bubble diagram is located at this link.